Institute for Evidence-Based Healthcare, Bond University, Gold Coast, Australia.
Gold Coast University Hospital, Gold Coast, Australia.
Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD009417. doi: 10.1002/14651858.CD009417.pub3.
Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019.
To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital.
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 2 December 2022) with no restrictions. We searched two trial registries for ongoing trials (to 2 December 2022) and checked the reference lists of reviews and included articles for additional studies.
Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence certainty using GRADE.
In total, we included eight trials involving 906 infants and children aged up to three years. We included one new trial in this update. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. Five trials were conducted at single or multiple sites within a single high-income country (four in the USA, one in Qatar). Three trials included study sites in different countries. All three of these trials included study sites in one or more high-income countries (USA, Chile, New Zealand, Australia, Qatar), with two trials also including a study site in a middle-income country (Panama). Five of the eight trials were "supported" or "sponsored" by the trial drug manufacturers. The evidence is very uncertain about the effect of immunoglobulins on mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 4 studies, 309 participants). There were four deaths - two amongst 98 children receiving immunoglobulins, and two amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however the study group of the child was not known and the data were not included in the analysis (very low-certainty evidence). The use of immunoglobulins in infants and children admitted to hospital with RSV proven LRTI probably results in little to no difference in the length of hospitalisation (mean difference (MD) -0.13 days, 95% CI -0.37 to 0.12; 6 studies, 737 participants; moderate-certainty evidence). Immunoglobulins may result in little to no difference in the number of children who experience one or more adverse events of any severity or seriousness compared to placebo (RR 1.18, 95% CI 0.78 to 1.78; 5 studies, 340 participants; low-certainty evidence) or the number of children who experience one or more adverse events judged by study investigators to be serious in nature, compared to placebo (RR 1.08, 95% CI 0.65 to 1.79; 4 studies, 238 participants; low-certainty evidence). Certainty of evidence for secondary outcomes was low. This evidence suggests that use of immunoglobulins results in little to no difference in the need for, or duration of, mechanical ventilation and the need for, or duration of, supplemental oxygen. The use of immunoglobulins does not reduce the need for admission to the intensive care unit (ICU) and when children are admitted to the ICU results in little to no difference in the duration of ICU stay.
AUTHORS' CONCLUSIONS: We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.
每年都有数百万人因呼吸道合胞病毒（RSV）感染而住院。治疗方法是支持性的，目前的治疗方法（例如吸入支气管扩张剂、肾上腺素、雾化高渗盐水和皮质类固醇）无效或效果有限。呼吸道合胞病毒免疫球蛋白可能被预防性用于预防 RSV 相关疾病导致的住院。它可能被考虑用于治疗已确诊的严重 RSV 感染或用于免疫功能低下的宿主的治疗，尽管它未获得此用途的许可。尚不清楚免疫球蛋白是否可改善已确诊 RSV 感染婴儿和幼儿住院治疗的结局。这是 2019 年首次发表的综述的更新。
评估免疫球蛋白治疗住院的 RSV 证实的下呼吸道感染（LRTI）的疗效，这些儿童年龄均不超过 3 岁。
对于 2022 年的这次更新，我们检索了 Cochrane 急性呼吸道感染专题检索库（CENTRAL），其中包含 Cochrane 急性呼吸道感染试验注册库、Ovid MEDLINE、Embase、CINAHL 和 Web of Science（从建库起至 2022 年 12 月 2 日），未设任何限制。我们检索了两项试验注册库（至 2022 年 12 月 2 日），并检查了综述和纳入文章的参考文献，以获取其他研究。
比较免疫球蛋白与安慰剂治疗经实验室诊断的 RSV 下呼吸道感染住院的婴儿和儿童（年龄不超过 3 岁）的随机对照试验。
两位综述作者独立选择试验、评估偏倚风险并提取数据。我们使用 GRADE 评估证据确定性。
总共纳入了 8 项试验，涉及 906 名年龄不超过 3 岁的婴儿和儿童。本更新纳入了一项新试验。这些试验中使用的免疫球蛋白制剂包括抗 RSV 免疫球蛋白以及单克隆抗体制剂 palivizumab 和 motavizumab。五项试验在一个高收入国家的一个或多个地点进行（四项在美国，一项在卡塔尔）。三项试验包括来自一个或多个高收入国家（美国、智利、新西兰、澳大利亚、卡塔尔）的研究地点，其中两项试验还包括一个中收入国家（巴拿马）的研究地点。八项试验中的五项是由试验药物制造商“支持”或“赞助”的。关于免疫球蛋白对死亡率的影响，证据非常不确定（风险比（RR）0.87，95%置信区间（CI）0.14 至 5.27；4 项研究，309 名参与者）。有 4 例死亡 - 2 例发生在接受免疫球蛋白治疗的 98 名儿童中，2 例发生在接受安慰剂治疗的 98 名儿童中。第四个试验中还发生了另外 1 例死亡，但患儿所在的研究组不详，数据未纳入分析（极低确定性证据）。在因 RSV 证实的 LRTI 而住院的婴儿和儿童中使用免疫球蛋白，可能导致住院时间的长短几乎没有差异（平均差值（MD）-0.13 天，95%CI -0.37 至 0.12；6 项研究，737 名参与者；中等确定性证据）。与安慰剂相比，免疫球蛋白可能导致任何严重程度的不良事件或严重程度的不良事件数量，或研究人员认为严重程度的不良事件数量，几乎没有差异（RR 1.18，95%CI 0.78 至 1.78；5 项研究，340 名参与者；低确定性证据），或由研究人员判断为严重程度的不良事件数量，几乎没有差异（RR 1.08，95%CI 0.65 至 1.79；4 项研究，238 名参与者；低确定性证据）。次要结局的证据确定性较低。这一证据表明，使用免疫球蛋白可能对机械通气的需求和持续时间、补充氧气的需求和持续时间几乎没有影响。免疫球蛋白的使用并不能减少入住重症监护病房（ICU）的需求，而当儿童入住 ICU 时，对 ICU 住院时间的影响也几乎没有。
我们对免疫球蛋白对死亡率的影响非常不确定。我们有一定的把握认为，在住院的婴儿和儿童中使用免疫球蛋白可能会使住院时间的长短几乎没有差异。免疫球蛋白可能对不良事件、机械通气的需求和持续时间、补充氧气的需求和持续时间、或入住 ICU 的需求几乎没有影响，不过我们对这方面的证据不太确定，免疫球蛋白对这些结局的实际效果可能与本综述中观察到的估计效果有很大差异。所有试验均在高收入国家进行，缺乏死亡率较高的 RSV 感染人群的数据。
